Project summary: Inflammatory responses are essential to enable the body to defend against infection and repair damaged tissue; however, abnormal inflammatory responses during pregnancy increase the risk of complications such as pre-eclampsia, fetal growth restriction, preterm labor, and gestational diabetes mellitus (GDM). The goal of this supplementary proposal is to examine the potential benefits of inflammatory suppression on uterine smooth muscle (Project 1) and the role of a lifestyle intervention involving diet and physical activity in reducing hyperglycemia and inflammation in GDM in minority women (Project 2). Abnormal uterine distension is associated with an increased risk of preterm delivery, and increased mechanical strain causes cellular stress and increases the risk of preterm labor. Our central hypothesis is that mechanical strain activates p38 MAPK signaling leading to cytokine secretion, myometrial activation, and increased risk of preterm labor. We expect to identify mechanisms by which excess uterine strain could prematurely drive myometrial activation and labor. GDM has been associated with elevated systemic inflammation and oxidative stress, and very few intervention trials have assessed the role of a lifestyle intervention in alleviating these pathological processes. Our central hypothesis is that dietary bioactive compounds and postprandial physical activity can improve GDM-related hyperglycemia and inflammation. We expect lifestyle intervention to improve hyperglycemia, oxidative stress and inflammation associated with GDM, and subsequently decrease the need for pharmacological intervention in these women.